Haemodialysis-associated amyloidosis: β2-microglobulin alone or associated with globin chains?

Argilés, Àngel; Mourad, Georges; Axelrud-Cavadore, Claude; Derancourt, Jean; Adell, J. Jauregui; Mion, C; Cavadore, Jean‐Claude

doi:10.1042/cs0730515

Cited by 19 publications

(9 citation statements)

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“…2 -M), other compounds which could have been present at the start of the procedure might have been overlooked. We J. M. Campistol and A. Argiles found that this could have been the case for globin chains [35].…”

Section: Technical Approachmentioning

confidence: 76%

“…We have identified the latter as being a 2 -macroglobulin [33]. We have also identified some of the remaining proteins found with TCA precipitation as being globin chains, light chains of immunoglobulins, and also albumin, haemopexin and transferrin [32,34,35]. The second aspect is the technical approach to analyse the protein solution after preparation.…”

Section: Technical Approachmentioning

confidence: 99%

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Dialysis-related amyloidosis: visceral involvement and protein constituents

Campistol

Argilés

1996

Nephrology Dialysis Transplantation

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beta 2-M amyloidosis mainly concerns dialysis patients and typically presents with osteoarticular symptoms. In order to precise the incidence and gravity of visceral involvement, subcutaneous abdominal fat aspirates, skin and rectal biopsies, as well as echocardiograms were performed in 26 patients with severe beta 2-M amyloidosis. Visceral amyloidosis was confirmed in 58% and the numbers were even higher when including heart abnormalities suggestive of amyloidosis (81%). Clinical manifestations of visceral involvement were usually not severe and include odynophagia, gastrointestinal haemorrhage, intestinal obstruction, kidney stones, myocardial dysfunction and subcutaneous tumours. The removal and synthesis rates of beta 2-M were assessed during dialysis. Serum 131I-beta 2-M levels decreased by 5-10% with cuprophane and by 40-45% with polysulfone and polyacrylonitrile membranes. These reduction rates were higher than those found with unlabelled beta 2-M suggesting an increased synthesis or release during dialysis. The protein constituents of amyloid deposits were studied. Two different preparative methods to extract the proteins from amyloid deposits were used. TCA precipitation showed the presence of several proteins which were not observed with PBS homogenizing and resuspending in guanidine. The protein constituents of amyloid fibrils were studied by both, two dimensional gel electrophoresis (2D-gel) as well as protein sequencing after gel filtration. Similarly, the technical approach used for protein analysis greatly influenced the results. It was observed that 2D-gel displayed the presence of proteins which were missed by the gel filtration technique. Some of the proteins contained in amyloid deposits in addition to beta 2-M, were identified as globin chains, kappa and lambda light chains of immunoglobulins, and alpha 2 macroglobulin. A putative participation of these other protein constituents on the pathogenesis of beta 2-microglobulin amyloidosis is discussed.

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Section: Technical Approachmentioning

confidence: 76%

Section: Technical Approachmentioning

confidence: 99%

Dialysis-related amyloidosis: visceral involvement and protein constituents

Campistol

Argilés

1996

Nephrology Dialysis Transplantation

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“…In addition, high-molecular-mass peaks above the ovalbumin marker were detected in both the /2m and HLA assays, and therefore contained Class I-associated fi2m. In the sera from the haemodialysis patients, an additional fl2m fraction was observed in a region where no HLA was detected (fractions [24][25][26][27][28]. As this peak may represent free ,f2m molecules associated in a dimeric form, a further characterization of free thin forms in such patients was carried out by immunopurification of fl2m.…”

Section: Resultsmentioning

confidence: 99%

“…[27] and Argiles et al [28] have isolated and sequenced the acidic forms of monomeric fl2m isolated from dialysis fluid and serum respectively of haemodialysis patients. We demonstrate for the first time in this paper the presence of a circulating dimeric form of f82m.…”

Section: Discussionmentioning

confidence: 99%

Molecular variants of β2-microglobulin in renal insufficiency

Vincent

Dennoroy²,

Révillard

1994

Biochemical Journal

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Many patients with renal insufficiency treated by dialysis for more than 10 years have tissue deposits of amyloid material containing polymerized beta 2-microglobulin (beta 2m). The mechanisms of beta 2m polymerization and degradation remain unknown. In biological fluids (serum and urine) from haemodialysis patients and in dialysis fluids from patients treated by chronic ambulatory peritoneal dialysis (CAPD), we have characterized different molecular forms of beta 2m, including proteolytic split products. beta 2m isoforms of pI 5.7, 5.3 and 4.5-5.0 were isolated from urine and CAPD fluid. The pI 5.3 beta 2m, but not the other forms, was recovered both as monomers and as dimers. Such dimers were also detected in serum from patients but not from healthy controls. pI 5.3 and 5.7 beta 2m isoforms were found to be nearly identical by mass spectrometry and by their amino acid sequences. The amino acid sequence of the 43 N-terminal amino acids of beta 2m of pI 5.0 showed identity with the corresponding region of pI 5.7 beta 2m. Fragments recovered from CAPD fluid were similar to proteolytic fragments generated from pure pI 5.7 beta 2m by incubation in mouse ascitic fluid at acidic pH. Furthermore, pure pI 5.7 beta 2m was converted into more acidic forms of 12 kDa upon incubation in mouse ascitic fluid at acid pH. beta 2m dimers found in serum may represent a precursor of amyloid fibrils.

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“…Linke et al [70, 71]observed proteolyzed β 2 -microglobulin in amyloid material from dialysis patients. However, most of the reports that have analyzed the sequence of β 2 -microglobulin suggest that proteolysis is not necessary to form amyloid deposits [10, 72, 73, 74, 75]. Subsequently, other forms of amyloidosis have also been found to have an intact N terminus of their major protein: atrial natriuretic factor [76, 77], AL [78], and AA [79]amyloidosis.…”

Section: β2-microglobulin-related Factors:the Agep Hypothesismentioning

confidence: 99%